This application is for 2 years of continued support of this Pulmonary Vascular SCOR grant entitled "The Pathophysiology of Pulmonary Edema," which includes multidisciplinary clinical and basic research projects concerned with two important clinical problems: pulmonary edema and pleural effusion. The objectives are to obtain new knowledge about the pathophysiology of liquid and protein exchange in the lungs and pleural spaces of experimental animals and man, and to use this knowledge to improve the diagnosis, treatment and prevention of pulmonary edema and pleural effusion in patients. To achieve these objectives, there are three research components and an administrative core unit. The key specific aims of the scientific projects are as follows: A-1: to develop and apply physiologic and biochemical tests that will identify from among the large number of patients at risk and who might have sustained acute lung injury, those who are actually destined to acquire clinical manifestations of pulmonary parenchymal damage, especially the severe pulmonary complication of sepsis called the Adult Respiratory Distress Syndrome; B-2: To examine the roles played by recently recognized circulating substances, cytokines and adhesion receptors, in the pathogenesis of certain forms of acute lung injury in sheep characterized by increased permeability pulmonary edema, especially that caused by infusions of endotoxin and live bacteria; and B- 3: to quantify the turnover of pulmonary liquid and protein in the lung and pleural space to obtain a more complete understanding of pulmonary liquid and protein exchange in health and disease. As documented in the supporting documents, considerable progress has been made during the 4 years of the present award, and the proposed projects represent logical extensions of the work already carried out by a group of investigators with a long tradition of successful interaction and productivity.